Multiple factors dictate target selection by Hfq-binding small RNAs.

Hfq-binding small RNAs (sRNAs) in bacteria modulate the stability and translational efficiency of target mRNAs through limited base-pairing interactions. While these sRNAs are known to regulate numerous mRNAs as part of stress responses, what distinguishes targets and non-targets among the mRNAs predicted to base pair with Hfq-binding sRNAs is poorly understood. Using the Hfq-binding sRNA Spot 42 of Escherichia coli as a model, we found that predictions using only the three unstructured regions of Spot 42 substantially improved the identification of previously known and novel Spot 42 targets. Furthermore, increasing the extent of base-pairing in single or multiple base-pairing regions improved the strength of regulation, but only for the unstructured regions of Spot 42. We also found that non-targets predicted to base pair with Spot 42 lacked an Hfq-binding site, folded into a secondary structure that occluded the Spot 42 targeting site, or had overlapping Hfq-binding and targeting sites. By modifying these features, we could impart Spot 42 regulation on non-target mRNAs. Our results thus provide valuable insights into the requirements for target selection by sRNAs.

The effects of diabetes mellitus on the corneal endothelium: A review.

The corneal endothelium plays a critical role in maintaining corneal clarity. There is an expected decline in cell density with age and disease, and maintaining the health of this cell layer is important as corneal endothelial cells generally are amitotic in vivo. Diabetes mellitus is a highly prevalent disease that damages the corneal endothelium. Diabetes causes structural and functional impairments in the corneal endothelium that decrease cellular reserve in response to stress. These effects have implications to consider for diabetic patients undergoing anterior segment surgery, and for corneal surgeons who use diabetic donor tissue and treat diabetic patients. In this review, we discuss the specifics of how diabetes mellitus impacts the corneal endothelium including alterations in cell morphology, cell density, ultrastructure, pump and barrier function, cataract surgery outcomes, and corneal transplant outcomes with attention to the use of diabetic donor tissue and diabetic transplant recipients.

Evaluation of interferon alpha 2b as adjunctive therapy for conjunctival melanoma.

PURPOSE: Interferon alpha 2b (IFN-α2b) has been used as an adjunctive agent to treat conjunctival melanoma (CM), however its efficacy is unproved due to a paucity of data. We present 5 cases of incompletely excised CM lesions to inform clinical decision making regarding the adjunctive use of IFN-α2b. OBSERVATIONS: We identified all biopsy proven CM cases treated between 1997 and 2017 at the University of Iowa. Of these, we analyzed cases in which topical IFN-α2b drops were prescribed after the initial excision to treat surgical margins that were positive for primary acquired melanosis [PAM] with or without atypia or invasive CM. We noted the origin of CM (nevus, PAM, or de novo), presence and location of margins positive for residual melanoma, duration of IFN-α2b treatment, recurrences, time to recurrence, and outcome at last follow-up. Topical IFN-α2b drops (1 million IU/mL 4 times daily for 3-6 months) were used as adjunctive therapy in 5 cases following incomplete surgical excision of CM. The preceding lesion was PAM in 4 cases and compound nevus in 1 case. In 2 cases, margins were positive for PAM with atypia and both resulted in remission of melanoma at 54 and 33 months, respectively. However, in 3 cases, margins were positive for invasive melanoma and all 3 developed recurrence of melanoma despite IFN-α2b use. CONCLUSIONS AND IMPORTANCE: There are limited data regarding the efficacy of IFN-α2b as adjunctive therapy for incomplete excision of CM lesions. In this series, adjunctive topical IFN-α2b did not prevent recurrence in cases with surgical margins positive for invasive melanoma. Our results indicate that caution should be exercised when considering adjunctive IFN-α2b to treat CM lesions not excised completely.

DMEK outcomes using nondiabetic grafts for recipients with diabetes mellitus.

PURPOSE: To compare Descemet membrane endothelial keratoplasty (DMEK) outcomes using nondiabetic grafts in diabetic and nondiabetic recipients. METHODS: All eyes that underwent DMEK between February 2013 and October 2016 (follow-up ≥3 months, without prior keratoplasty) were included. Recipients were divided into diabetic (insulin dependent [IDDM] or noninsulin dependent [NIDDM]) and nondiabetic groups. Main outcome measures included postoperative visual acuity, rebubble procedure rates, and graft failure rates. RESULTS: Of 334 eyes (243 subjects) included for analysis, 63 eyes (18.8%) were from diabetic recipients. At each timepoint, best-corrected visual acuity trended lower for IDDM recipients compared to NIDDM and nondiabetic recipients. There were no statistically significant differences in rebubble rates of diabetic compared to nondiabetic recipients (20.6% vs. 12.9%, p = 0.17), or IDDM compared to nondiabetic recipients (27.3% vs. 12.9%, p = 0.08; hazard ratio 2.26). Overall, 13 grafts (3.9%) failed (mean follow-up, 565 days; range, 90-1293 days). Graft failures did not differ between diabetic and nondiabetic recipients (4.0% vs. 4.9%, p = 0.15) regardless of subgroup (p = 0.36). CONCLUSIONS: DMEK provides excellent outcomes for patients with and without diabetes. DMEK outcomes were excellent with improvements in visual acuity and low rates of graft failure. Our findings were unable to determine differences between rebubble procedure rates but do emphasize the need for further research using stratified groups based on diabetes severity.

Glaucoma-associated corneal endothelial cell damage: A review.

The corneal endothelium is critical in maintaining a healthy and clear cornea. Corneal endothelial cells have a significant reserve function, but preservation of these cells is paramount as they have limited regenerative capacity. Glaucoma is a prevalent disease, and damage to the corneal endothelium may be caused by the disease process itself as well as by its treatment. The mechanisms involved in glaucoma-associated damage to the corneal endothelium need further investigation. Understanding how glaucoma and glaucoma surgery impact the endothelium is important for protecting corneal clarity and visual acuity in all glaucoma patients, including those undergoing corneal transplant. We will discuss a range of identified factors that may impact corneal endothelial cell health in glaucoma, including intraocular pressure, glaucoma medications, surgical glaucoma management, mechanical forces, and alterations in the aqueous environment.

Surgical management of pterygium.

Pterygia are noncancerous growths of conjunctiva that may require surgical removal because of discomfort, cosmesis, or obstruction of vision. Pterygia often recur after excision. The major goal of pterygium treatment is avoiding recurrence, but complication rates and cosmetic results are also considered. Despite the number of techniques available, there is no consensus on the best procedure. Even the best techniques carry risk of recurrence and complications. In this review, different surgical techniques, graft attachment methods, and adjuvant therapies in current use are discussed. Also discussed are newer techniques that early studies have shown to be promising, but require more investigation before becoming a recommended treatment. The review is intended to provide an overview of the current research to inform surgeons with regard to their decisions and aid researchers in hypothesis generation.